Following ingestion and entry into the gastrointestinal (Gl) tract, poliovirus, a human neurotropic enterovirus of Picornaviridae, may replicate in gastrointestinal-associated lymphatic tissues (GALT) and, subsequently, spread to the systemic circulation and to the CNS. Numerous attempts to study oral poliovirus infection in transgenic mice have so far failed. A focus of this application is to construct a novel transgenic mouse model for oral poliovirus infection that can be used to determine the site(s) of poliovirus proliferation in the Gl tract. A second focus of this application is to study mechanism(s) by which poliovirus is migrating in polarized tissue culture cells, in cells of neuronal origin, and in axons. Experiments have been developed based on our hypothesis that an interaction between the poliovirus receptor CD155 and Tctex-1, a cargo binding polypeptide of the dynein motor complex, is responsible for movement of poliovirus along microtubules.